Caldesmon: A calmodulin — Binding actin — Regulatory protein

The protein caldesmon, originally isolated from smooth muscle tissue where it is the most abundant calmodulin-binding protein, has since been shown to have a wide distribution in actin- and myosin- containing cells where it is localized in sub-cellular structures concerned with motility, shape changes and exo- or endo-cytosis. Caldesmon is believed to be an actin- regulatory protein, and binds with high affinity to actin or actin-tropomyosin. Caldesmon inhibits the activation by actin-tropomyosin of myosin MgATPase activity, and the inhibition can be reversed by Ca2+.calmodulin. The binding of caldesmon to smooth muscle proteins has been studied in detail, enabling a model to be constructed which could account for the observed Ca2+ regulation of smooth muscle thin filaments. The abundance of caldesmon, and the Ca2+-regulation of its activity via calmodulin, mean that it is potentially an important intracellular regulator of processes such as smooth muscle contraction, cell motility and secretion.     

“Infant Mortality in Armenia 1992–2003”: A comment

The purpose of this comment is to counsel caution in some of the conclusions drawn in an otherwise fine article recently published in Economics and Human Biology on infant mortality in Armenia by Hakobyan, Mkrtchyan and Yepiskoposyan. These relate first, to the reliability of estimates and trends in infant mortality estimated from DHS data; second, to the interpretation of what the authors consider to be a ‘low’ infant mortality rate in former communist countries given their level of economic development; and third, to the role of the health care infrastructure in countries of the former Soviet Union in producing these ‘low’ infant mortality levels. This comment argues that trends in infant mortality in Armenia and other CIS countries, although probably declining, are perhaps less certain than the authors allow, that existing evidence does not suggest that they are uniformly low by global standards, or that the health care systems in CIS countries are uniformly effective in reducing infant deaths.     

New Caledonia: A ‘ Hot Spot’ for Valuable Chemodiversity

The flora of New Caledonia encompasses more than 3000 plant species and almost 80% are endemic. New Caledonia is considered as a ‘hot spot’ for biodiversity. With the current global loss of biodiversity and the fact that several drugs and pesticides become obsolete, there is an urgent need to increase sampling and research on new natural products. In this context, we review the chemical knowledge available on New Caledonian native flora from economical perspectives. We expect that a better knowledge of the economic potential of plant chemistry will encourage the plantation of native plants for the development of a sustainable economy which will participate in the conservation of biodiversity. In the second part of this review, we focus on the results exposed in 60 scientific articles and describe the identification of 225 original compounds from basal angiosperms and eudicot rosids. We discuss the economic potential of plants and molecules from medicinal and industrial perspectives. This review also highlights several plants and groups, such as Amborella sp., Piperaceae, or Phyllanthaceae, that are unexplored in New Caledonia despite their high chemical interest. Those plants are considered to have priority in future chemical investigations.     

Human α‐amino‐β‐carboxymuconate‐ε‐semialdehyde decarboxylase (ACMSD): A structural and mechanistic unveiling

Human α‐amino‐β‐carboxymuconate‐ε‐semialdehyde decarboxylase determines the fate of tryptophan metabolites in the kynurenine pathway by controlling the quinolinate levels for de novo nicotinamide adenine dinucleotide biosynthesis. The unstable nature of its substrate has made gaining insight into its reaction mechanism difficult. Our electron paramagnetic resonance (EPR) spectroscopic study on the Cu‐substituted human enzyme suggests that the native substrate does not directly ligate to the metal ion. Substrate binding did not result in a change of either the hyperfine structure or the super‐hyperfine structure of the EPR spectrum. We also determined the crystal structure of the human enzyme in its native catalytically active state (at 1.99 Å resolution), a substrate analogue‐bound form (2.50 Å resolution), and a selected active site mutant form with one of the putative substrate binding residues altered (2.32 Å resolution). These structures illustrate that each asymmetric unit contains three pairs of dimers. Consistent with the EPR findings, the ligand‐bound complex structure shows that the substrate analogue does not directly coordinate to the metal ion but is bound to the active site by two arginine residues through noncovalent interactions. Proteins 2015; 83:178–187. © 2014 Wiley Periodicals, Inc.     

Synthesis and Enzymatic Deprotection of Fully Protected 2′‐5′ Oligoadenylates (2‐5A): Towards a Prodrug Strategy for Short 2‐5A

Fully protected pA2′p5′A2′p5′A trimers 1a and 1b have been prepared as prodrug candidates for a short 2′‐5′ oligoadenylate, 2‐5A, and its 3′‐O‐Me analog, respectively. The kinetics of hog liver carboxyesterase (HLE)‐triggered deprotection in HEPES buffer (pH 7.5) at 37° has been studied. The deprotection of 1a turned out to be very slow, and 2‐5A never appeared in a fully deprotected form. By contrast, a considerable proportion of 1b was converted to the desired 2‐5A trimer, although partial removal of the 3′‐O‐[(acetyloxy)methyl] group prior to exposure of the adjacent phosphodiester linkage resulted in 2′,5′→3′,5′ phosphate migration and release of adenosine as side reactions.     

Intrinsic α‐helical and β‐sheet conformational preferences: A computational case study of alanine

A fundamental question in protein science is what is the intrinsic propensity for an amino acid to be in an α-helix, β-sheet, or other backbone dihedral angle (-ψ) conformation. This question has been hotly debated for many years because including all protein crystal structures from the protein database, increases the probabilities for α-helical structures, while experiments on small peptides observe that β-sheet-like conformations predominate. We perform molecular dynamics (MD) simulations of a hard-sphere model for Ala dipeptide mimetics that includes steric interactions between nonbonded atoms and bond length and angle constraints with the goal of evaluating the role of steric interactions in determining protein backbone conformational preferences. We find four key results. For the hard-sphere MD simulations, we show that (1) β-sheet structures are roughly three and half times more probable than α-helical structures, (2) transitions between α-helix and β-sheet structures only occur when the backbone bond angle τ (N–C_α–C) is greater than 110°, and (3) the probability distribution of τ for Ala conformations in the “bridge” region of-ψ space is shifted to larger angles compared to other regions. In contrast, (4) the distributions obtained from Amber and CHARMM MD simulations in the bridge regions are broader and have increased τ compared to those for hard sphere simulations and from high-resolution protein crystal structures. Our results emphasize the importance of hard-sphere interactions and local stereochemical constraints that yield strong correlations between -ψ conformations and τ.     

A novel red‐emitting phosphor,KAl1‐xPO4Cl:Eux3+ (0.1 ≤ x ≤ 1.0)

A series of phosphors KAl_1‐xPO₄Cl:Eu_x³⁺ (0.1 ≤ x ≤ 1.0) was synthesized using a facile combustion method using urea as a fuel and their structural, morphological and photoluminescence properties were investigated. It was found that the particle size was in the range of 1–2 µm with an irregular shape. The f–f transitions of Eu³⁺ in the host lattice were assigned and discussed. The excitation and emission spectra indicated that this phosphor can be efficiently excited by ultraviolet (395 nm), and exhibit reddish orange emission corresponding to the ⁵D₀→⁷F_J (J = 0, 1, 2) transitions of Eu³⁺. The impact of the Eu³⁺ concentration on the relative emission intensity was investigated, and the best doping concentration is 0.5. The present study suggests that the KAl_0.5PO₄Cl: Eu_0.5³⁺ phosphor is a strong candidate as a red component for phosphor‐ converted white light‐emitting diodes (LEDs). Copyright © 2015 John Wiley & Sons, Ltd.     

Alpha‐2‐macroglobulin: A physiological guardian

Alpha macroglobulins are large glycoproteins which are present in the body fluids of both invertebrates and vertebrates. Alpha‐2‐macroglobulin (α₂M), a key member of alpha macroglobulin superfamily, is a high‐molecular weight homotetrameric glycoprotein. α₂M has many diversified and complex functions, but it is primarily known by its ability to inhibit a broad spectrum of proteases without the direct blockage of the protease active site. α₂M is also known to be involved in the regulation, transport, and a host of other functions. For example, apart from inhibiting proteinases, it regulates binding of transferrin to its surface receptor, binds defensin and myelin basic protein, etc., binds several important cytokines, including basic fibroblast growth factor (bFGF), platelet‐derived growth factor (PDGF), nerve growth factor (NGF), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6), and modify their biological activity. α₂M also binds a number of hormones and regulates their activity. α₂M is said to protect the body against various infections, and hence, can be used as a biomarker for the diagnosis and prognosis of a number of diseases. However, this multipurpose antiproteinse is not “fail safe” and could be damaged by reactive species generated endogenously or exogenously, leading to various pathophysiological conditions. J. Cell. Physiol. 228: 1665–1675, 2013. © 2012 Wiley Periodicals, Inc.     

A new paradigm in cell therapy for diabetes: Turning pancreatic α‐cells into β‐cells

Cell therapy means treating diseases with the body's own cells. One of the cell types most in demand for therapeutic purposes is the pancreatic β‐cell. This is because diabetes is one of the major healthcare problems in the world. Diabetes can be treated by islet transplantation but the major limitation is the shortage of organ donors. To overcome the shortfall in donors, alternative sources of pancreatic β‐cells must be found. Potential sources include embryonic or adult stem cells or, from existing β‐cells. There is now a startling new addition to this list of therapies: the pancreatic α‐cell. Thorel and colleagues recently showed that under circumstances of extreme pancreatic β‐cell loss, α‐cells may serve to replenish the insulin‐producing compartment. This conversion of α‐cells to β‐cells represents an example of transdifferentiation. Understanding the molecular basis for transdifferentiation may help to enhance the generation of β‐cells for the treatment of diabetes.     

Upslope movements and large scale expansions: the taxonomy and biogeography of the Coenonympha arcania –C. d arwiniana –C. gardetta butterfly species complex

Sibling species groups are suitable models for the understanding of inter‐ and intraspecific processes in taxonomy and biogeography. We analysed 262 individuals from the Alps of the Coenonympha arcania/gardetta species complex by allozyme electrophoresis. These taxa showed high variance amongst populations (F_ST: 0.391) and strong intertaxon genetic differentiation (F_CT: 0.376). Although morphologically similar, Coenonympha gardetta and Coenonympha arcania clearly differ in their genetic characteristics; the morphologically intermediate taxa Coenonympha darwiniana darwiniana and Coenonympha darwiniana macromma are genetically well distinguished from each other and the two other taxa. Coenonympha arcania and C. d. macromma most probably share a common ancestor and evolved by cladogenesis, whereas the taxonomic situation of C. d. darwiniana is still unresolved: This taxon might be the result of hybridization between C. arcania and C. gardetta or it might have a common ancestor together with C. gardetta. We suggest species rank for all four taxa. The distribution of genetic diversity of these populations and the differentiation amongst populations suggest rather different biogeographical scenarios: C. arcania most probably is of Mediterranean origin with postglacial range expansion northwards; C. gardetta survived the last ice age in peripheral refugia of the Alps and has spread all over this high mountain system in the postglacial; C. darwiniana and C. macromma survived the Würm in geographic proximity to their actual distribution areas and only have performed moderate uphill translocations during postglacial warming. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 159 , 890–904.